The Clinical Molecular Profiling Core (CMPC) is a collaborative core that seeks to go beyond the common service paradigm of other cores. The expertise of the personnel allows us to be involved from the start of a project, such as the protocol development, though performance of the assay and biostatistical analysis. Currently, our main function is to support clinical trials at the National Cancer Institute (NCI) and to that end we have collaborations with many of the branches in the Center for Cancer Research (CCR) and the Clinical Center. Many dozen clinical collaborations have involved many of the branches in CCR such as Medical Oncology, Dermatology, Urologic Oncology, Laboratory of Pathology, Pediatric Oncology, Metabolism, and Radiation Oncology. The status of these collaborations range from preliminary discussions through protocol development, accrual and analysis, and completion. For those that are completed, we look forward to being involved in follow up studies. Many of the studies are clinical trials testing drugs in phase I or II or new combination therapies. These include studies such as Sorafenib and Bevacizumab in Treating Patients With Refractory, Metastatic or Unresectable Solid Tumors; Pan-HER Inhibitor PF-00299804 in Non-Small Cell Lung Cancer; a Group Wide Biology and Banking Study for Phase II Studies of R1507; Phase II Study of Belinostat in Patients With Recurrent or Metastatic Unresectable Thymoma or Thymic Carcinoma Previously Treated With Prior Platinum-Containing Chemotherapy; Phase I/II trial of Vandetanib (ZD6474 Zactima) in Children and Adolescents with Hereditary Medullary Thyroid Carcinoma; Identifying Genomic Aberrations in Pediatric Pontine Glioma; Phase I Study of the AKT inhibitor Triciribine Phosphate Monohydrate and Erlotinib (Tarceva) in Subjects with Advanced Lung Cancer or other Solid Tumors Who are Resistant to or Naive to Epidermal Growth Factor Receptor (EGFR) Inhibitors; Phase II trial in patients with stage IV melanoma for lapatinib treatment when they are ERBB4 mutation carriers; Targeted Phase I Trial of ZD6474 (Vandetanib AZCTIMA) plus the Proteasome Inhibitor Bortezomib (Velcade) in Adults with Solid Tumors with a Focus on Hereditary or Sporadic, Locally Advanced or Metastatic Medullary Thyroid Cancer (MTC); Clinical identification of gene mutations clinical GIST; Genotype-directed anti-MAPK pathway therapy in pancreas cancer; Genomic testing of germline renal cancer genes; and a Pilot Trial of Molecular Profiling and Targeted Therapy for Advanced Non-Small Cell Lung Cancer, Small Cell Lung Cancer, and Thymic Malignancies. However, other investigations are more focused on understanding the underlying pathology of specific diseases and are not directly testing a therapy. These studies include: Gene Expression Profiling and Phototoxicity in Adults and Children Exposed to Ultraviolet Radiation; Clinical Evaluations and Laboratory Studies in Patients With Chronic Graft-Versus-Host Disease Who Have Undergone a Stem Cell Transplant; Clinical Manifestations and Molecular Bases of Heritable Urologic Malignant Disorders; Collection of Serum and Tissue Samples From Patients With Biopsy-Proved or Suspected Malignant Disease; Large Scale Methylation Analysis of Follicular Lymphoma; Molecular Profiling of Small Cell Lung Cancer; Molecular Profiling of Thymoma Subsets; Leukemia Biology Study; Esophageal Carcinoma in China; Laser Capture Microdissection and Evaluation of the Microenvironment in Prostate Cancer; Immunotoxin Resistance in Patients with Hairy Cell Leukemia; Understanding the methylation changes and subtypes in glioma stem cells derived from glioblastoma; The natural history of Medullary Thyroid Carcinoma, particularly in patients with MEN 2, and the molecular pathways involved in tumorigenesis and the development of resistance to targeted therapies; Analysis of global DNA methylation in breast tumors of African-American and European-American patients; Examine the association between risk of familial chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis; and Biomarkers and Radiation Side Effects in Patients Undergoing Radiation Therapy for Gastrointestinal Cancer. In the last year eight additional collaborations have been added and they include: A Phase II Study of Ponatinib in Advanced or Metastatic Medullary Thyroid Cancer; A Feasibility Study using COXEN Algorithm for Individualized Therapeutic-Sensitivity Prediction in Patients with Advanced Urothelial Cancer; Phase II trial of the gamma-secretase inhibitor PF-03084014 in adults with desmoid tumors/aggressive; and Telomere length and methylation in hepatocellular carcinoma. Significantly, resources have begun to be devoted to actualizing clinical exome sequencing using Illumina next-generation sequencers. To support these studies, the CMPC has expertise in many molecular technologies for the analysis of DNA and RNA from human specimens. State of the art assays found on a wide range of advanced platforms include: DNA sequencing (Sanger and next-generation sequencing), mRNA expression analysis (microarray, real-time PCR, bead-based), epigenomic methylation (microarray and pyrosequencing), array comparative genomic hybridization (microarray), and telomere length assays. Importantly, the CMPC provides full bioinformatics support for all these assays.